Of the 3 species of Echinococcus that cause hydatid disease in man, E. granulosus has two distinct biological forms. The more pathogenic, maintained by synanthropic hosts, forms local variants or "strains," attributed by some to clone-formation and other reproductive peculiarities. The neotropical E. vogeli is highly pathogenic, but its public health significance is undefined. E. multilocularis is the cause of alveolar hydatid disease (AHD), a severe and often lethal infection important in much of the northern hemisphere. Regarded as an emerging zoonosis in various regions, AHD in the United States mainly affects Eskimos in western Alaska, where the mortality is about 70% of cases. Chemotherapy with drugs of the benzimidazole group is beneficial, based on a 10-year clinical trial in Eskimo patients. Albendazole has been substituted for mebendazole because of greater therapeutic promise. Prevention of AHD depends on adequate epidemiological data, not now available. The proposed work would continue investigations in progress by the P.I. since 1949, and would emphasize: 1) Summary and computer-analysis of information derived from a long-term, intensive study (1956-1974) of the epidemiology of E. multilocularis on St. Lawrence Island (Alaska), under natural and hyperendemic conditions. At least 6 papers planned during the grant-period would provide information useful in devising methods of prevention and control. The study is unique, and would also provide information of basic scientific value. 2) Evaluation of lesions from patients, with or without therapy, would continue, using histological, immunohistochemical, and other methods, to contribute to better diagnosis, to evaluate chemotherapy, and to contribute to management of patients. 3) Cytogenetic studies of Echinococcus spp. would continue, using Giemsa-banding and other methods to define affinities and to elucidate reproductive processes in cestodes. 4) The description of post-larval development of E. vogeli would contribute to basic knowledge of a pathogen. 5) Effects of long-term passage of E. multilocularis in respective species of rodents would define rate and extent of strain-formation. These investigations are interrelated, and can be efficiently conducted concurrently.